Eu(OTf)₃‑Catalyzed Highly Regioselective Nucleophilic Ring Opening of 2,3-Epoxy Alcohols: An Efficient Entry to 3‑Substituted 1,2-Diol Derivatives

In our study of the total synthesis of (+)-irciniastatin A, we found a need to develop a method that enables a C3-selective nucleophilic ring opening of 2,3-epoxy alcohol by MeOH, by which we found that the use of combined catalytic amounts of Eu­(OTf)₃ and 2,6-di-<i>tert</i>-butyl-4-methylpyridine (DTBMP) enables the intended transformation to obtain 3-methoxy-1,2-diol efficiently. Promising features of a protocol that effects a highly regioselective nucleophilic ring opening of 2,3- and 3,4-epoxy alcohols using various nucleophiles including alcohols, thiols, and unprotected amines are described

Total Synthesis and Biological Evaluation of Irciniastatin A (a.k.a. Psymberin) and Irciniastatin B

Irciniastatin A (a.k.a. psymberin) and irciniastatin B are members of the pederin natural product family, which have potent antitumor activity and structural complexity. Herein, we describe a full account of our total synthesis of (+)-irciniastatin A and (−)-irciniastatin B. Our synthesis features the highly regioselective Eu­(OTf)₃-catalyzed, DTBMP-assisted epoxide ring opening reaction with MeOH, which enabled a concise synthesis of the C1–C6 fragment, extensive use of AZADO (2-azaadamantane <i>N</i>-oxyl) and its related nitroxyl radical/oxoammonium salt-catalyzed alcohol oxidation throughout the synthesis, and a late-stage assembly of C1–C6, C8–C16, and C17–C25 fragments. In addition, for the synthesis of (−)-irciniastatin B, we achieved the C11-selective control of the oxidation stage via regioselective deprotection and AZADO-catalyzed alcohol oxidation. The synthetic irciniastatins showed high levels of cytotoxic activity against mammalian cells. Furthermore, chemical footprinting experiments using synthetic compounds revealed that the binding site of irciniastatins is the E-site of the ribosome